The Long Range Plan of the National Institute of Arthritis and Musculoskeletal and Skin Diseases places a high priority on the relationship between behavioral and social factors and the outcomes of chronic diseases. Behavioral and social factors strongly influence the ability of patients to conduct self-care. Poor self-care may adversely affect the management of diabetic foot ulcers, the major factor leading to 85,000 amputations annually in the U.S. My research focuses on how a behavioral factor (depression) affects a prevalent chronic skin condition (diabetic foot ulcers), leading to a disabling outcome (amputation). In diabetes, depression is associated with impaired self-care and the development of multiple complications, including death. It is not yet known if depression is a risk factor for lower extremity amputation. It is plausible that depression could result in a higher risk of amputation through decreased self- care in the setting of foot ulcers. The aims of our study are to test whether diagnosed depression is associated with incident lower extremity amputation in patients with diabetes and whether certain covariates related to self-care will mediate the relationship between diagnosed depression and amputation. Our hypotheses will be tested through a retrospective cohort study design using a national Veterans Administration database, the Diabetes Epidemiology Cohort. A greater understanding of the relationship between depression and lower extremity amputation could have a significant impact on public health by improving foot ulcer care and preventing amputations. If we find an association between depression and amputation, we will next investigate how depression affects self-care in patients with diabetic foot ulcers. This knowledge will allow us to design a depression treatment for foot ulcer patients that will be integrated into a future clinical trial of diabetic foot ulcer care.